The studies proposed in this grant application exemplify a continuation and extension of our ongoing work on the isolation, characterization and expression of new families of endogenous retroviruses. To this end, we plan to isolate and characterize a purportedly novel class of human endogenous retroviruses that we have identified with avian retrovirus-specific genetic probes that we have previously used to identify new classes of avian endogenous retroviruses. Our proposed studies include: (1) isolation of the avian retrovirus-related human endogenous virus family by molecular cloning and characterization by nucleotide sequence analysis; (2) characterization of the extent and nature of expression of this additional family of human endogenous retroviruses in normal and malignant human cell types; and (3) a comparison of this novel endogenous retrovirus family as well as the other previously identified families of human endogenous retroviruses with "C" type virion particles produced by various human tumors including testicular germ cell tumors and differentiating populations of embryonal carcinoma cells to determine whether the "C" type particles produced by these germ cell tumors exhibit any sequence homology to any of the families of human endogenous viruses. The methodologies that we plan to employ to achieve these objectives are, for the most part, already implemented in our laboratory and include a variety of physiochemical, enzymological and hybridization techniques available for the analysis of DNA, RNA, and protein, including nucleotide sequence analysis.